Short-term treatment with IL21 and GSK-3β inhibition to produce higher quality CD8+ T cells 4583

Description INTRODUCTION High quality T cells are critical to induce effective anti-tumor responses. Treatment with IL21 and GSK-3β inhibitors has shown substantial promise at improving T cell activities. We sought to better characterize the impacts of these treatments on T cell quality. METHODS & RESULTS To evaluate the impact of IL21 and GSK-3β inhibitor (TWS119) on CD8+ T cell quality, T cells were stimulated and proliferated for 10 days in the presence of IL7, IL15 and the agents. A higher proportion of less differentiated CD8+ T cells was obtained with IL21 and TWS119. However, a full 10 days of treatment with these agents resulted in low viability and cell numbers and decreased metabolic activity. Short-term treatment, specifically for the first 2-4 days did not induce negative effects, but instead made the CD8+ T cells remain less differentiated, and this phenotype persisted after removal of the agents. DISCUSSION Even though IL21 and TWS119 were beneficial to concentrate CD8+ T cells into a less differentiated population, prolonged treatment did not yield favorable results. Alternatively, short-term exposure with the agents also resulted in less differentiated T cells but displayed significant improvements in T cell quality. Further experiments with tumors are warranted to uncover functional profiles of the CD8+ T cells. CONCLUSION Short-term treatment with IL21 and TWS119 show the potential to improve quality of CD8+ T cells. Funding Sources This research was supported with funding from the Intramural Research Program of the National Cancer Institute.